This invited technical review article takes a look back and a look ahead in the area of research and development for international safeguards: some main developments, applications, the lessons learned and the outlook for the future. Selected highlights of the past scientific and technical contributions of the European Commission's Joint Research Centre to the International Atomic Energy Agency safeguards inspections and technical support divisions are described: the development of the first large-sized metal spikes, the delivery of a laboratory robot designed for automatic U/Pu separations, the provision of safeguards training in PERLA (Performance Laboratory) and the use of the TEMPEST (Thermal, Electro-Magnetic, Physical Equipment Stress Testing) laboratory for IAEA. Current collaborations include the support activities to the Rokkasho Reprocessing plant, work on environmental micro-particle analysis, the delivery of nuclear reference materials and ultrasonic seals and the support in combating illicit trafficking of nuclear and radioactive materials. Based on these collaborations, an analysis is presented of the lessons learned and the areas for potential improvement, both under the support programme scheme and through enhanced international collaboration. Finally an outlook of future challenges and opportunities is given for S&T support to international safeguards and nuclear security issues, covering aspects such as exploitation of satellite imagery and open source information, enhanced instruments for physical inventory taking in U facilities, innovative applications of containment and surveillance technologies, novel training courses for enhancing the nuclear inspectors observation and soft skills and issues of proliferation resistance of future nuclear energy systems.